Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, but Middle Eastern adults are under-represented in cohorts reporting Oxford MEST-C (mesangial, endocapillary, segmental, tubular atrophy/interstitial fibrosis, and crescent) lesions, limiting region-specific histologic risk profiling. We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review of observational adult (≥18 years) primary IgAN cohorts from Middle Eastern countries reporting Oxford MEST or MEST-C. MEDLINE (PubMed), Embase, and Scopus were searched from January 1, 2009, to November 24, 2025, with no language restrictions; citation searching (backward reference screening and forward citation tracking) was also performed. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale (NOS). For each MEST-C component, we calculated descriptive pooled proportions by summing numerators and denominators across cohorts with available extractable data; renal outcomes were synthesized narratively. Four retrospective cohorts (total n=528) from Iran, Turkey, and Saudi Arabia met eligibility criteria. Three cohorts contributed extractable lesion counts for M1, S1, and T1-2 (E1 data were available in two cohorts). Descriptive pooled frequencies were: mesangial hypercellularity (M1) 80.0%, endocapillary hypercellularity (E1) 35.7%, segmental glomerulosclerosis (S1) 58.5%, and tubulointerstitial scarring (T1-2) 56.4%. Crescent reporting was limited; where extractable, C≥1 was 28.9% in the Turkish cohort, and a sensitivity approximation incorporating a study reporting overall crescent frequency yielded ~27.6%. Where reported, T and crescent lesions were associated with worse renal outcomes. Formal heterogeneity testing and quantitative outcome meta-analysis were not performed due to a few clinically diverse cohorts. Risk of bias was low-to-moderate, mainly due to retrospective design, convenience sampling, and incomplete outcome reporting. Available Middle Eastern cohorts show frequent M1 and S1, with substantial T1-2 scarring and crescents in a sizeable minority of biopsied patients. These findings likely reflect advanced histologic injury at biopsy in tertiary-care cohorts and/or variation in case mix and biopsy/referral practices, underscoring the need for prospective regional registries with standardized pathology reporting and outcome definitions.